This proposal describes 8 projects in synthesis of congeners of indole alkaloids with established high biological activities. 1. Synthesis of non-cytotoxic pro-drugs, which are site selectively activated by atropisomeric (conformational) inversion to provide vinblastine-type anticancer compounds. 2. Synthesis of anticancer pro-drugs based upon high antimicrotubule activity but have the requirement of site selected activation for cell membrane penetration. 3. Synthesis of anti-multidrug resistance compounds derived from stereoisomers of vinblastine-type yohimbe-type and strychnos-type alkaloids. 4. Synthesis of vindolinine congeners as potential anti-AIDS agents. 5. Synthesis of the potent anticancer marine alkaloid manzamine-A. 6. Studies in new synthetic methodology that can be used in the above projects as well as in other syntheses of complex structures.